Pharmacogenomics of Hypertension and Heart Disease

Arwood, Meghan J.; Cavallari, Larisa H.; Duarte, Julio D.

doi:10.1007/s11906-015-0586-5

Cited by 22 publications

(18 citation statements)

References 94 publications

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“…89,90 Identification of PGx markers for beta blockers, thiazide diuretics and angiotensin-converting enzyme inhibitors for the treatment of hypertension and heart failure has been on the focus of intense research for the past two decades and the reader is referred to recent reviews in this area. 91–93 …”

Section: Future Challengesmentioning

confidence: 99%

Pharmacogenetics in Cardiovascular Medicine

Tuteja

Limdi

2016

Curr Genet Med Rep

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Purpose of review Pharmacogenetics is an important component of precision medicine. Even within the genomic era, several challenges lie ahead in the road towards clinical implementation of pharmacogenetics in the clinic. This review will summarize the current state of knowledge regarding pharmacogenetics of cardiovascular drugs, focusing on those with the most evidence supporting clinical implementation- clopidogrel, warfarin and simvastatin. Recent findings There is limited translation of pharmacogenetics into clinical practice primarily due to the absence of outcomes data from prospective, randomized, genotype-directed clinical trials. There are several ongoing randomized controlled trials that will provide some answers as to the clinical utility of genotype-directed strategies. Several academic medical centers have pushed towards clinical implementation where the clinical validity data are strong. Their experiences will inform operational requirements of a clinical pharmacogenetics testing including the timing of testing, incorporation of test results into the electronic health record, reimbursement and ethical issues. Summary Pharmacogenetics of clopidogrel, warfarin and simvastatin are three examples where pharmacogenetics testing may provide added clinical value. Continued accumulation of evidence surrounding clinical utility of pharmacogenetics markers is imperative as this will inform reimbursement policy and drive adoption of pharamcogenetics into routine care.

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Section: Future Challengesmentioning

confidence: 99%

Pharmacogenetics in Cardiovascular Medicine

Tuteja

Limdi

2016

Curr Genet Med Rep

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“…In view of the facts that elevated blood pressure has evolved as the leading contributor to global burden of disease [ 1 , 2 ] and unsatisfactory control rates achieved by antihypertensive drug treatment [ 3 , 4 ], there is an urgent need for more effective ways to individualize drug therapies in a patient-specific fashion. While pharmacogenomics approaches may be well suited for personalized treatment of the rare varieties of monogenic hypertension [ 5 , 6 ], studies on pharmacogenomics of essential hypertension have shown much less progress [ 7 , 8 ]. Recent genome-wide association studies on genetic associations of specific antihypertensive drug responses have revealed several potential gene loci of interest [ 9 – 16 ], but the data so far published have lacked consistently replicated findings, and presently there appears to be no clinically useful genetic markers to guide the choice of a given blood pressure-lowering drug.…”

Section: Introductionmentioning

confidence: 99%

Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension

et al. 2017

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ObjectiveIn order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles.MethodsMetabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings.ResultsAmlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10−5) and losartan (P values down to 2 x 10−4) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation.ConclusionsAlthough this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.

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“…The most commonly used antihypertensive drugs in clinical practice are β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers and diuretics. In this context, several pharmacogenetic studies presented evidences on multiple genetic variants (Table 2) associated with response to antihypertensive drugs (68)(69)(70). In this context, several pharmacogenetic studies presented evidences on multiple genetic variants (Table 2) associated with response to antihypertensive drugs (68)(69)(70).…”

Section: Pharmacogenetics Of Antihypertensive Drugsmentioning

confidence: 98%

Cardiovascular pharmacogenetics: a promise for genomically‐guided therapy and personalized medicine

Zaiou

Amri

2016

Clinical Genetics

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Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered. Evidence suggests that genetic defects could influence CVD development and inter-individual responses to widely used cardiovascular drugs like clopidogrel, aspirin, warfarin, and statins, and therefore, they may be integrated into clinical practice. If clinically validated, better understanding of these genetic variations may provide new opportunities for personalized diagnostic, pharmacogenetic-based drug selection and best treatment in personalized medicine. However, numerous gaps remain unsolved due to the lack of underlying pathological mechanisms for how genetic predisposition could contribute to CVD. This review provides an overview of the extraordinary scientific progress in our understanding of genetic and genomic basis of CVD as well as the development of relevant genetic biomarkers for this disease. Some of the actual limitations to the promise of these markers and their translation for the benefit of patients will be discussed.

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Pharmacogenomics of Hypertension and Heart Disease

Cited by 22 publications

References 94 publications

Pharmacogenetics in Cardiovascular Medicine

Pharmacogenetics in Cardiovascular Medicine

Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension

Cardiovascular pharmacogenetics: a promise for genomically‐guided therapy and personalized medicine

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